The enzymic hydrolysis of proteins within lysosomes of animal cells produces free amino acids which normally transit the lysosomal membrane to the exterior milieu at a rapid rate. In studies conducted over the past several years we have obtained evidence that transport of the amino acid cystine from lysosomes of normal human polymorphonuclear leucocytes occurs by way of a stereospecific, carrier-mediated process exhibiting saturation kinetics. No exodus of cystine can be detected from corresponding lysosomes isolated from patients afflicted with the inherited childhood disorder cystinosis, a potentially fatal disease characterized by excessive storage of cystine, but of no other amino acid, within the lysosomes of many tissues. The maximum velocity of cystine egress from lysosomes of obligate heterozygotes for cystinosis was found to be one-half that of normal, indicating that clinically unaffected carriers possess half the normal complement of the putative cystine carrier. These observations constitute presumptive evidence for a defective lysosomal cystine carrier as the underlying cause of human cystinosis. More recent studies have been directed to the further characterization of the lysosomal cystine carrier system. It has been found that cystine egress from normal polymorphonuclear leucocytes is stimulated by ATP in the presence of potassium ions. This stimulation is not affected by agents known to block the ATP- dependent lysosomal proton pump (e.g., N-ethylmaleimide, ammonium ions or the protonophore CCCP) and thus appears to be due to a mechanism other than acidification per se, possibly to phosphorylation of the cystine carrier.